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Genome-wide Purification of Extrachromosomal Circular DNA from Eukaryotic Cells
Published on: April 4, 2016
Amplificación de genes histónicos por la formación de cromosomas circulares en Saccharomyces cerevisiae
1Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
Nature
|October 27, 2006
Resumen
Cuando los genes de histona H2A-H2B (HTA1-HTB1) se eliminan en la levadura, la célula amplifica los genes de histona restantes (HTA2-HTB2) creando un nuevo cromosoma circular para mantener la integridad genómica.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Genética La genética.
- Biología de la levadura Biología de la levadura.
Sus antecedentes:
- Los niveles de histona son cruciales para los procesos celulares fundamentales, incluida la transcripción y la segregación cromosómica.
- En la levadura (Saccharomyces cerevisiae), las histonas H2A y H2B están codificadas por dos pares de genes: HTA1-HTB1 y HTA2-HTB2.
- Anteriormente se sabía que la compensación transcripcional por HTA1-HTB1 ocurría cuando se elimina HTA2-HTB2.
Objetivo del estudio:
- Investigar mecanismos alternativos de compensación de la dosis del gen de la histona más allá de la regulación transcripcional.
- Para dilucidar el proceso por el cual se mantiene el número de copia del gen histona cuando se elimina HTA1-HTB1.
Principales métodos:
- La eliminación del par de genes HTA1-HTB1 en Saccharomyces cerevisiae.
- Análisis de los eventos de replicación y recombinación del ADN, en particular los que involucran retrotransposones Ty1.
- Caracterización de los cromosomas circulares recién formados utilizando técnicas moleculares.
Principales resultados:
- La eliminación de HTA1-HTB1 desencadena la compensación del número de copias genéticas, no solo el ajuste transcripcional.
- Se forma un nuevo y pequeño cromosoma circular que contiene HTA2-HTB2, HHT1-HHF1 (locus de la histona H3-H4), un centrómero y orígenes de replicación.
- La recombinación entre los elementos Ty1 flanqueantes impulsa la formación de este cromosoma amplificado que contiene el gen de la histona, que ocurre a una tasa más alta en los mutantes hta1-htb1Delta.
Conclusiones:
- La disminución de los niveles de las histonas H2A y H2B estimulan específicamente la amplificación de los genes de la histona a través del ADN extracromosómico.
- Este mecanismo de amplificación génica asegura el mantenimiento de la dosis del gen de la histona y la integridad genómica.
- Demuestra una nueva forma de compensación de dosis a nivel del número de copias genéticas en respuesta al agotamiento de las histonas.
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